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Research articles in the clinical and translational science literature commonly use quantitative data to inform evaluation of interventions, learn about the etiology of disease, or develop methods for diagnostic testing or risk prediction of future events. The peer review process must evaluate the methodology used therein, including use of quantitative statistical methods. In this manuscript, we provide guidance for peer reviewers tasked with assessing quantitative methodology, intended to complement guidelines and recommendations that exist for manuscript authors. We describe components of clinical and translational science research manuscripts that require assessment including study design and hypothesis evaluation, sampling and data acquisition, interventions (for studies that include an intervention), measurement of data, statistical analysis methods, presentation of the study results, and interpretation of the study results. For each component, we describe what reviewers should look for and assess; how reviewers should provide helpful comments for fixable errors or omissions; and how reviewers should communicate uncorrectable and irreparable errors. We then discuss the critical concepts of transparency and acceptance/revision guidelines when communicating with responsible journal editors.
We investigate when a Legendrian knot in the standard contact ${{\mathbb{R}}}^3$ has a non-orientable exact Lagrangian filling. We prove analogs of several results in the orientable setting, develop new combinatorial obstructions to fillability, and determine when several families of knots have such fillings. In particular, we completely determine when an alternating knot (and more generally a plus-adequate knot) is decomposably non-orientably fillable and classify the fillability of most torus and 3-strand pretzel knots. We also describe rigidity phenomena of decomposable non-orientable fillings, including finiteness of the possible normal Euler numbers of fillings and the minimisation of crosscap numbers of fillings, obtaining results which contrast in interesting ways with the smooth setting.
Social cognition has not previously been assessed in treatment-naive patients with chronic schizophrenia, in patients over 60 years of age, or in patients with less than 5 years of schooling.
Methods
We revised a commonly used measure of social cognition, the Reading the Mind in the Eyes Test (RMET), by expanding the instructions, using both self-completion and interviewer-completion versions (for illiterate respondents), and classifying each test administration as ‘successfully completed’ or ‘incomplete’. The revised instrument (RMET-CV-R) was administered to 233 treatment-naive patients with chronic schizophrenia (UT), 154 treated controls with chronic schizophrenia (TC), and 259 healthy controls (HC) from rural communities in China.
Results
In bivariate and multivariate analyses, successful completion rates and RMET-CV-R scores (percent correct judgments about emotion exhibited in 70 presented slides) were highest in HC, intermediate in TC, and lowest in UT (adjusted completion rates, 97.0, 72.4, and 49.9%, respectively; adjusted RMET-CV-R scores, 45.4, 38.5, and 34.6%, respectively; all p < 0.02). Stratified analyses by the method of administration (self-completed v. interviewer-completed) and by education and age (‘educated-younger’ v. ‘undereducated-older’) show the same relationship between groups (i.e. NC>TC>UT), though not all differences remain statistically significant.
Conclusions
We find poorer social cognition in treatment-naive than in treated patients with chronic schizophrenia. The discriminant validity of RMET-CV-R in undereducated, older patients demonstrates the feasibility of administering revised versions of RMET to patients who may otherwise be considered ineligible due to education or age by changing the method of test administration and carefully assessing respondents' ability to complete the task successfully.
The foetal programming hypothesis posits that optimising early life factors e.g. maternal diets can help avert the burden of adverse childhood outcomes e.g. childhood obesity. To improve applicability to public health messaging, we investigated whether maternal whole diet quality and inflammatory potential influence childhood adiposity in a large consortium.
Methods
We harmonized and pooled individual participant data from up to 8,769 mother-child pairs in 7 European mother-offspring cohorts. Maternal early-, late-, and whole-pregnancy dietary quality and inflammatory potential were assessed with Dietary Approaches to Stop Hypertension (DASH) and energy-adjusted Dietary Inflammatory Index (E-DII), respectively. Primary outcome was childhood overweight and obesity (OWOB), defined as age- and sex-specific body-mass-index-z score (BMIz) > 85th percentile based on WHO growth standard. Secondary outcomes were sum-of-skinfold-thickness (SST), fat-mass-index (FMI) and fat-free-mass-index (FFMI) in available cohorts. Outcomes were assessed in early- [mean (SD) age: 2.8 (0.3) y], mid- [6.2 (0.6) y], and late-childhood [10.6 (1.2) y]. We used multivariable regression analyses to assess the associations of maternal E-DII and DASH with offspring adiposity outcomes in cohort-specific analyses, with subsequent random-effects meta-analyses. Analyses were adjusted for maternal age, pre-pregnancy BMI, parity, lifestyle factors, energy intake, educational attainment, offspring age and sex.
Results
A more pro-inflammatory maternal diet, indicated by higher E-DII, was associated with a higher risk of offspring late-childhood OWOB [pooled-OR (95% CI) comparing highest vs. lowest E-DII quartiles: 1.22 (1.01,1.47) for whole-pregnancy and 1.38 (1.05,1.83) for early-pregnancy; both P < 0.05]. Moreover, higher late-pregnancy E-DII was associated with higher mid-childhood FMI [pooled-β (95% CI): 0.11 (0.003,0.22) kg/m2; P < 0.05]; trending association was observed for whole-pregnancy E-DII [0.12 (-0.01,0.25) kg/m2; P = 0.07]. A higher maternal dietary quality, indicated by higher DASH score, showed a trending inverse association with late-childhood OWOB (pooled-OR (95% CI) comparing highest vs. lowest DASH quartiles: 0.58 (0.32,1.02; P = 0.06). Higher early-pregnancy DASH was associated with lower late-childhood SST [pooled-β (95% CI): -1.9 (-3.6,-0.1) cm; P < 0.05] and tended to be associated with lower late-childhood FMI [-0.34 (-0.71,0.04) kg/m2; P = 0.08]. Higher whole-pregnancy DASH tended to associate with lower early-childhood SST [-0.33 (-0.72,0.06) cm; P = 0.10]. Results were similar when modelling DASH and E-DII continuously.
Discussion
Analysis of pooled data suggests that pro-inflammatory, low-quality maternal antenatal diets may influence offspring body composition and obesity risk, especially during mid- or late-childhood. Due to variation of data availability at each timepoint, our results should be interpreted with caution. Because most associations were observed at mid-childhood or later, future studies will benefit from a longer follow-up.
Prediction of future changes in dynamics of the Earth’s ice sheets, mass loss and resultant contribution to sea-level rise are the main objectives of ice-sheet modeling. Mass transfer from ice sheet to ocean is, in large part, through outlet glaciers. Subglacial topography plays an important role in ice dynamics; however, trough systems have not been included in bed digital elevation models (DEMS) used in modeling, because their size is close to the model resolution. Using recently collected CReSIS MCoRDs data of subglacial topography and an algorithm that allows topographically and morphologically correct integration of troughs and trough systems at any modeling scale (5 km resolution for SeaRISE), an improved Greenland bed DEM was developed that includes Jakobshavn Isbræ, Helheim, Kangerdlussuaq and Petermann glaciers (JakHelKanPet DEM). Contrasting the different responses of two Greenland ice-sheet models (UMISM and SICOPOLIS) to the more accurately represented bed shows significant differences in modeled surface velocity, basal water production and ice thickness. Consequently, modeled ice volumes for the Greenland ice sheet are significantly smaller using the JakHelKanPet DEM, and volume losses larger. More generally, the study demonstrates the role of spatial modeling of data specifically as input for dynamic ice-sheet models in assessments of future sea-level rise.
The Bering Glacier–Bagley Icefield system in Alaska is currently surging (2011). Large-scale elevation changes and small-scale elevation-change characteristics are investigated to understand surge progression, especially mass transport from the pre-surge reservoir area to the receiving area and propagation of the kinematic surge wave as manifested in heavy crevassing characteristic of rapid, brittle deformation. This analysis is based on airborne laser altimeter data collected over Bering Glacier in September 2011. Results include the following: (1) Maximal crevasse depth is 60 m, reached in a rift that separates two deformation domains, indicative of two different flow regimes. Otherwise surge crevasse depth reaches 20–30 m. (2) Characteristic parameters of structural provinces are derived by application of geostatistical classification. Parameters include significance and spacing of crevasses, surface roughness and crevasse-edge curvature (indicative of crevasse age). A classification based on these parameters serves to objectively discriminate structural provinces, indicative of surge progression down-glacier and up-glacier. (3) Elevation changes from 2011 and 2010 altimetry show 40–70 m surface lowering in the reservoir area in lower central Bering Glacier and 20–40m thickening near the front in Tashalich arm. Combining elevation changes with results of crevasse profilometry and pattern analysis, the rapid progression of the surge can be mathematically–physically reconstructed.
Dynamic ice-sheet models are used to assess the contribution of mass loss from the Greenland ice sheet to sea-level rise. Mass transfer from ice sheet to ocean is in a large part through outlet glaciers. Bed topography plays an important role in ice dynamics, since the acceleration from the slow-moving inland ice to an ice stream is in many cases caused by the existence of a subglacial trough or trough system. Problems are that most subglacial troughs are features of a scale not resolved in most ice-sheet models and that radar measurements of subglacial topography do not always reach the bottoms of narrow troughs. The trough-system algorithm introduced here employs mathematical morphology and algebraic topology to correctly represent subscale features in a topographic generalization, so the effects of troughs on ice flow are retained in ice-dynamic models. The algorithm is applied to derive a spatial elevation model of Greenland subglacial topography, integrating recently collected radar measurements (CReSIS data) of the Jakobshavn Isbræ, Helheim, Kangerdlussuaq and Petermann glacier regions. The resultant JakHelKanPet digital elevation model has been applied in dynamic ice-sheet modeling and sea-level-rise assessment.
Our objective is to map dynamic provinces and investigate dynamic changes in Jakobshavn Isbræ, Greenland. We use an approach that combines structural glaciology and remote-sensing data analysis, facilitated by mathematical characterization of generalized spatial surface roughness that provides parameters related to ice dynamics, deformation and interaction of the ice with bed topography. The approach is applied to derive time series of elevation and roughness changes and to attribute changes during rapid retreat. Different dynamic types of fast- and slow-moving ice can be mapped from ICESat Geoscience Laser Altimeter System data (2003–09) and Airborne Topographic Mapper data, using spatial roughness characterization, validated with ASTER and bed-topographic data. Results of comparative analysis of elevation changes and roughness changes of Jakobshavn south ice stream indicate (1) surface lowering of 10–15 m a-1 between 2004 and 2009 and (2) no change in surface roughness and dynamic types. These findings are consistent with a front retreat as part of a fjord-glacier cycle or following warming of fjord water and with climatic warming, but not with an internal dynamic acceleration as a cause of the observed changes during rapid retreat. Relationships to changes in basal water pressure are discussed. All glaciodynamic changes appear to have initiated near the front and propagated up-glacier.
Annual bluegrass is a weed species in turfgrass environments known for exhibiting resistance to multiple herbicide modes of action, including photosystem II (PSII) inhibitors. To evaluate populations of annual bluegrass for susceptibility to PSII inhibitors of varied chemistries, populations were treated with herbicides from triazolinone, triazine, and substituted urea families: amicarbazone, atrazine, and diuron, respectively. Sequencing of the psbA gene confirmed the presence of a Ser264 to Gly amino acid substitution within populations that exhibited resistance to both atrazine and amicarbazone. A single biotype, DR3, which lacked any previously reported psbA gene point mutation, exhibited resistance to diuron, atrazine, and amicarbazone. DR3 had a significantly lower rate of absorption and translocation of atrazine and had enhanced atrazine metabolism when compared with both the Ser264 to Gly resistant mutant and susceptible biotypes. We thus report possible nontarget mechanisms of resistance to PSII-inhibiting herbicides in annual bluegrass.
Repeat rectal chlamydia infection is common in men who have sex with men (MSM) following treatment with 1 g azithromycin. This study describes the association between organism load and repeat rectal chlamydia infection, genovar distribution, and efficacy of azithromycin in asymptomatic MSM. Stored rectal chlamydia-positive samples from MSM were analysed for organism load and genotyped to assist differentiation between reinfection and treatment failure. Included men had follow-up tests within 100 days of index infection. Lymphogranuloma venereum and proctitis diagnosed symptomatically were excluded. Factors associated with repeat infection, treatment failure and reinfection were investigated. In total, 227 MSM were included – 64 with repeat infections [28·2%, 95% confidence interval (CI) 22·4–34·5]. Repeat positivity was associated with increased pre-treatment organism load [odds ratio (OR) 1·7, 95% CI 1·4–2·2]. Of 64 repeat infections, 29 (12·8%, 95% CI 8·7–17·8) were treatment failures and 35 (15·4%, 95% CI 11·0–20·8) were reinfections, 11 (17·2%, 95% CI 8·9–28·7) of which were definite reinfections. Treatment failure and reinfection were both associated with increased load (OR 2·0, 95% CI 1·4–2·7 and 1·6, 95% CI 1·2–2·2, respectively). The most prevalent genovars were G, D and J. Treatment efficacy for 1 g azithromycin was 83·6% (95% CI 77·2–88·8). Repeat positivity was associated with high pre-treatment organism load. Randomized controlled trials are urgently needed to evaluate azithromycin's efficacy and whether extended doses can overcome rectal infections with high organism load.
Feedlot management systems for beef cattle are becoming a more common practice in Australia reflecting opportunities to ensure quality of product whilst maintaining cost efficiencies within production. However, feedlot systems have been identified as point sources of greenhouse gases emissions (GGE: methane, nitrous oxide and the indirect greenhouse gas ammonia). It has been estimated that feedlot systems contribute 3.5% of total direct methane emissions (Alford et al. 2006), and 30% of total emissions from livestock wastes. Furthermore, approximately 1% of total N2O emissions from agriculture are attributed to livestock. This paper reports methane, N2O and NH3 emissions from an Australian feedlot system managed under summer climatic conditions. It compares actual measured emissions with estimated from three recognised models used by national governments to estimate total GGE per annum from livestock agriculture.
where . Let e ∈ ℝ2 with |e| = 1. If u(x, 0) is smooth, bounded and
we prove u → e uniformly in x as t → ∞. Of particular interest is the motion of the zeros (vortices) of u. In this case, all zeros disappear after a finite time.
This work addresses the need for thick layers of ferroelectric thin films on semiconductors for integrated optics applications. The deposition of BaTiO3 thin films with MgO buffers on patterned GaAs substrates is presented as an approach to achieve crack-free optical waveguiding structures. Cracking and peeling of the thin films are observed on patterns with lateral dimensions exceeding 60 microns and nearly crack-free thin films for patterns with lateral dimensions of a few microns. The cracking and peeling of the thin films is attributed to thermal expansion mismatch during the heating and cooling steps of the deposition process. A thin film stress and fracture model is used to analyze the phenomenon. Reduced cracking and peeling on the patterned features are attributed to strain relief on the patterned features. The inclusion of thick AlxOy buffer layers obtained through wet-oxidation of AlGaAs prior to BaTiO3/MgO deposition are presented as a means of obtaining electro-optic waveguide structures on GaAs.
During RNA interference (RNAi), long dsRNA is processed to ∼21 nt duplexes, short interfering RNAs (siRNAs), which silence genes through a mRNA degradation pathway. Small temporal RNAs (stRNAs) and micro-RNAs (miRNAs) are ∼21 nt RNAs that are processed from endogenously encoded hairpin-structured precursors, and function to silence genes via translational repression. Here we report that synthetic hairpin RNAs that mimic siRNAs and miRNA precursor molecules can target a gene for silencing, and the mechanism of silencing appears to be through mRNA degradation and not translational repression. The sequence and structural configuration of these RNAs are important, and even slight modification in structure can affect the silencing activity of the hairpins. Furthermore, these RNAs are active when expressed by DNA vectors containing polymerase III promoters, opening the possibility for new approaches in stable RNAi-based loss of function studies.
A low-power, atmospheric pressure, microwave plasma torch was used to make spherical alumina particles of controlled size from irregularly shaped precursor powders. Detailed studies of the impact of operating parameters, particularly gas identity (argon or air), gas flow rates, and applied power, showed that particle size changed in a predictable fashion. The most important factor in controlling particle size appears to be precursor particle density in the aerosol stream that enters the plasma hot zone. This and other facts suggest that particle collision rate is primarily responsible for determining ultimate particle size, although atomic addition also plays a role. Reproducible volume average particle sizes ranging from 97 to 1150 μm3 were formed from precursor particles of order 14 μm3. Moreover, for the first time we report the creation of an atmospheric pressure low-power air plasma (<1 kW).
The mean radial velocity of NGC 288 (accuracy 5.5 km/s) is determined to be −56.3 ± 20.1 km/s which, when combined with the mean proper motion (Guo, 1995), yields a peculiar velocity with respect to the LSR of (u,v,w) = (29.7 ± 18.1, −258.6 ± 18.3,62.3 ± 20.3) km/s. This implies that NGC 288 moves in a retrograde sense with the Galactic rotation. We also derived the effective temperatures for stars in our sample and, as a corroborative effort, compared with those estimated previously from the BATC data (Tsai 1998) by spectral energy distribution fitting. We demonstrate that the BATC/SED fitting is an appropriate and efficient way to estimate the effective temperature of a star.